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AIMS: Gastrointestinal (GI) dysfunction, as a common peripheral-organ complication after traumatic brain injury (TBI), is primarily characterized by gut inflammation and damage to the intestinal mucosal barrier (IMB). Previous studies have confirmed that TongQiao HuoXue Decoction (TQHXD) has strong anti-inflammatory properties and protects against gut injury. However, few have reported on the therapeutic effects of TQHXD in a TBI-induced GI dysfunction model. We aimed to explore the effects of TQHXD on TBI-induced GI dysfunction and the underlying mechanism thereof. METHODS: We assessed the protective effects and possible mechanism of TQHXD in treating TBI-induced GI dysfunction via gene engineering, histological staining, immunofluorescence (IF), 16S ribosomal ribonucleic acid (rRNA) sequencing, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and flow cytometry (FCM). RESULTS: TQHXD administration ameliorated TBI-induced GI dysfunction by modulating the abundance and structure of bacteria; reconstructing the destroyed epithelial and chemical barriers of the IMB; and improving M1/M2 macrophage, T-regulatory cell (Treg)/T helper 1 cell (Th1 ), as well as Th17 /Treg ratios to preserve homeostasis of the intestinal immune barrier. Notably, Cluster of Differentiation 36 (CD36)/15-lipoxygenase (15-LO)/nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling was markedly stimulated in colonic tissue of TQHXD-treated mice. However, insufficiency of both CD36 and (C-X3-C motif) chemokine receptor 1 (CX3CR1) worsened GI dysfunction induced by TBI, which could not be rescued by TQHXD. CONCLUSION: TQHXD exerted therapeutic effects on TBI-induced GI dysfunction by regulating the intestinal biological, chemical, epithelial, and immune barriers of the IMB, and this effect resulted from the stimulation of CD36/NR4A1/15-LO signaling; however, it could not do so when CX3CR1 and CD36 were deficient. TQHXD might therefore be a potential drug candidate for treating TBI-induced GI dysfunction.

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Lesiones Traumáticas del Encéfalo , Medicamentos Herbarios Chinos , Enfermedades Gastrointestinales , Ratones , Animales , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Transducción de Señal , Linfocitos T Reguladores , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico

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ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

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Arteria Basilar , Proteínas Señalizadoras YAP , Ratones , Femenino , Animales , Arteria Basilar/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factores de Transcripción/metabolismo , Atorvastatina/farmacología

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Traditional Chinese medicine has emerged as promising targets for ischemic stroke (IS) therapy, yet the mechanism remains elusive. The current study was performed with an aim to investigate the action and mechanism of Tongqiao Huoxue decoction (TQHXD) affecting the neurological impairment secondary to IS based on network pharmacology. Based on network pharmacology and bioinformatics analysis, target genes and pathways involved in the treatment of TQHXD against IS were predicted. Serum containing TQHXD was prepared through blood collection from C57BL/6 mice after intragastric administration of TQHXD. The main results exhibited that Prostaglandin-endoperoxide synthase 2 (PTGS2) exhibited an abundance in IS and enrichment in the NF-kappa B signaling pathway, holding the potential as targets related to TQHXD treatment for IS. TQHXD was found to rescue cell viability, inhibit apoptosis, and alleviate inflammation under oxygen and glucose deprivation and reoxygenation (OGD/R) exposure. Furthermore, our in vivo experiment validated the protective function of TQHXD in ischemic brain damage stimulated by middle cerebral artery occlusion (MCAO). This protective action of TQHXD could be attenuated by overexpressing nuclear factor (NF)-kappa B, which was dependent on PTGS2. Collectively, TQHXD was demonstrated to ameliorate IS-induced neurological impairment by blocking the NF-kappa B signaling pathway and down-regulating PTGS2.

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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratones , Animales , FN-kappa B/metabolismo , Ciclooxigenasa 2/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal/genética , Accidente Cerebrovascular/genética , Isquemia Encefálica/genética

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To investigate the protective effect of Tongqiao Huoxue Decoction containing cerebrospinal fluid(TQHXD-CSF) on HT22 cells damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) and whether the mechanism is related to the regulation of ASK1/MKK4/JNK signaling pathway. HT22 cells were subjected to OGD/R to simulate cerebral ischemia-reperfusion injury(CIRI). Then the cells were randomly divided into five groups: blank cerebrospinal fluid(control group), OGD/R group, TQHXD-CSF group, Z-VAD-FMK group(20 µmol·L~(-1)) and TQHXD-CSF+Z-VAD-FMK group. Except the control group, cells in the other groups were reoxygenated for 12 h after 6 h of oxygen and glucose deprivation for modeling OGD/R, and group administration was performed. Cell viability and cytotoxicity were detected by CCK8 and LDH assay kit, respectively and the morphology of HT22 cells was observed by inverted microscope. Western blot and qRT-PCR were employed to detect the protein and mRNA expression levels of Bax, Bcl-2 and caspase-3, respectively. Then HT22 cells were assigned into the control group, OGD/R group, si-NC group, si-ASK1 group, TQHXD-CSF group and TQHXD-CSF+si-ASK1 group. Cell viability, proliferation and apoptosis were determined by CCK8, electric cell-substrate impedance sensing(ECIS), and Hoechst staining and flow cytometry, respectively. The protein expression of MKK4, p-MKK4, JNK, p-JNK, c-Jun, p-c-Jun, Cyt C, Bax, Bcl-2 and caspase-3 was tested by Western blot. The results showed that compared with OGD/R group, TQHXD-CSF significantly enhanced cell viability, improved cell morphology and reduced the protein and mRNA expression levels of Bax, Bcl-2 and caspase-3. In addition, when ASK1 was silenced, compared with OGD/R group, TQHXD-CSF remarkably improved cell viability, and decreased apoptosis rate and the protein expression levels of p-MKK4, p-JNK, p-c-Jun, Cyt C, Bax/Bcl-2 and caspase-3, but the effect was not as good as that of TQHXD-CSF+si-ASK1 group. In conclusion, TQHXD-CSF can inhibit apoptosis mediated by ASK1/MKK4/JNK signaling pathway in OGD/R-damaged HT22 cells, and has protective effect on ischemia-reperfusion injury.

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Sistema de Señalización de MAP Quinasas , Daño por Reperfusión , Humanos , Apoptosis , Proteína X Asociada a bcl-2/metabolismo , Caspasa 3/metabolismo , Glucosa , Oxígeno/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Daño por Reperfusión/metabolismo , ARN Mensajero/metabolismo

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Background: Intracerebral hemorrhage (ICH) is a type of stroke which results in a high disability and mortality rate and has a poor prognosis. Tongqiao Huoxue Decoction (TQHXD) is a classical Chinese prescription. Clinical practice has proven that TQHXD can promote blood circulation and can effectively treat ICH and its sequelae. However, the current mechanism is still unclear. Methods: The chemical components and target genes of TQHXD were collected from the Traditional Chinese medicine (TCM) Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine analysis platforms, and the gene expression data of ICH tissues were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to obtain differentially co-expressed gene pairs and build a drug-target-disease network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the obtained target genes and shared genes. Finally, molecular docking was carried out to further clarify the utility of TQHXD for the treatment of ICH. Results: A total of 304 differentially expressed genes in ICH, 42 TQHXD active ingredients, and 279 predicted targets of its active compounds were obtained. Bioinformatics analysis showed that they were involved in angiogenesis, the regulation of wound healing, and other biological processes. Furthermore, their participation in fluid shear stress and the atherosclerosis signaling pathway indicated their close association with the pathological processes of ICH. Finally, molecular docking was carried out to further confirm the tightly binding structural sites of the effective components of TQHXD and key proteins. Conclusions: In summary, the results of this study suggest that the mechanism of action of TQHXD in the treatment of ICH involves multiple targets and signaling pathways related to its occurrence and development. This study not only provides a new theoretical basis for the treatment of ICH with traditional Chinese medicine, but also provides new ideas for the research and development of drugs for the treatment of ICH.

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Ischaemic stroke (IS) is a common type of stroke characterised by sudden fainting and communication disorders, alongside a number of other symptoms. It is characterised by high morbidity, disability, and mortality rates. Tongqiao Huoxue Decoction (THD) is effective in the treatment of stroke. As a representative prescription for promoting blood circulation and removing blood stasis, THD has been widely used clinically. This paper systematically introduces clinical and experimental studies of THD in the treatment of IS, summarising its clinical application, pharmacological mechanisms, and active components in the treatment of IS. It also explores its key pathways in the treatment of IS through network pharmacology analyses, thereby speculating on its underlying mechanisms. It is of great significance for the secondary development of this classic prescription as well as for the research and development of new drugs.

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Investigación Biomédica/tendencias , Isquemia Encefálica/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Animales , Isquemia Encefálica/metabolismo , Medicamentos Herbarios Chinos/farmacología , Humanos , Accidente Cerebrovascular Isquémico/metabolismo , Resultado del Tratamiento

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Objective:To observe and compare the protective effects of Tongqiao Huoxue decoction （TQHX） prepared by three methods against cerebral ischemia-reperfusion injury （CIRI）， and to explore its mechanism through the glutamate （Glu） metabolic pathway in astrocytes. Method:The male SD rats of SPF grade were subjected to CIRI model induction by the modified middle cerebral artery occlusion method. The model rats were randomly divided into a model group， a sham operation group， and water-decocted， wine-decocted， and alcohol-extracted TQHX （6.3 g·kg^-1·d^-1） groups. The rats were treated correspondingly for 7 days. Those in the sham operation group and the model group were treated with an equal volume of normal saline by gavage. After the final treatment， the neurological function of rats was assessed by the modified neurological severity score （mNSS）. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of ischemic brain tissues in rats. High-performance liquid chromatography （HPLC） was used to detect glutamate （Glu） in ischemic brain tissues. The expression of glutamate transporter-1 （GLT-1） and glial fibrillary acidic protein （GFAP） and co-expression of glutamine synthetase （GS） and GFAP in ischemic brain tissues were detected by immunofluorescence assay. Western blot was used to detect the protein expression of GFAP， GLT-1， and GS. Result:Compared with the sham operation group， the model group showed increased mNSS （<italic>P</italic><0.01）， large necrosis of cerebral cortex in ischemic brain tissues with disordered cell arrangement， obscure boundary， intracellular edema， and inflammatory infiltration， elevated Glu in ischemic brain tissues （<italic>P</italic><0.01）， declining GLT-1-GFAP co-expression and GS-GFAP co-expression （<italic>P</italic><0.01）， up-regulated expression of GFAP protein， and reduced protein expression of GLT-1 and GS（<italic>P<</italic>0.05，<italic>P<</italic>0.01）. Compared with the model group， the TQHX groups showed decreased mNSS （<italic>P<</italic>0.01）， relieved injury in the cerebral cortex and hippocampal nerve cells in ischemic brain tissues， reduced Glu expression（<italic>P<</italic>0.05，<italic>P<</italic>0.01）， elevated co-expression of GLT-1 and GFAP （<italic>P<</italic>0.05，<italic>P<</italic>0.01）， and up-regulated protein expression of GFAP and GLT-1（<italic>P<</italic>0.05，<italic>P<</italic>0.01）. The co-expression of GS and GFAP （<italic>P<</italic>0.05，<italic>P<</italic>0.01）and the expression of GS （<italic>P<</italic>0.01）were increased in the wine-decocted and alcohol-extracted TQHX groups. Compared with the water-decocted TQHX group， the alcohol-extracted group showed increased GLT-1-GFAP and GS-GFAP co-expression（<italic>P<</italic>0.05）； the wine-decocted and alcohol-extracted TQHX groups exhibited elevated GS protein expression （<italic>P<</italic>0.05）； the alcohol-extracted TQHX group displayed declining Glu content （<italic>P</italic><0.01） and increased protein expression of GFAP and GLT-1 （<italic>P<</italic>0.05， <italic>P<</italic>0.01）. Compared with the wine-decocted TQHX group， the alcohol-extracted TQHX group showed increased protein expression of GFAP and GLT-1（<italic>P<</italic>0.05，<italic>P<</italic>0.01）. Conclusion:TQHX prepared by three methods can improve neurological deficits in CIRI rats. The effect is presumedly achieved by promoting the further activation of astrocytes， increasing the expression of GLT-1 and GS， promoting the clearance of Glu accumulated in the synaptic cleft by astrocytes through the Glu-glutamine （Gln） circulation， and reducing the excitotoxicity of Glu. The alcohol-extracted TQHX group was superior to the water-decocted and wine-decocted TQHX groups in reducing the content of Glu in ischemic brain tissues， promoting the activation of astrocytes， and enhancing the protein expression of GLT-1 and GS.

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Objective:To explore the clinical effects of Xingshen Tongqiao Huoxue decoction in the treatment of dysphagia caused by cricopharyngeal achalasia （CPA） after cerebral infarction and its influence on neurotransmitters. Method:One hundred and fourteen eligible patients were randomly divided into a control group （56 cases） and a treatment group （58 cases）. Patients in both groups received balloon catheter dilatation and rehabilitation training. In the observation group， the Tiandan Tongluo capsules were further orally taken， five capsales per time， three times per day. In the control group， the Xingshen Tongqiao Huoxue decoction was provided， one dose per day. The treatment lasted for four weeks. Following the videofluoroscopic swallow study （VFSS） and water-swallowing test （WST） before and after treatment， the swallowing quality of life questionnaire （SWAL-QOL）， functional oral intake scale （FOIS） and National Institutes of Health Stroke Scale （NIHSS） scores were calculated. The serum brain-derived neurotrophic factor （BDNF）， substance P （SP）， dopamine （DA）， 5-hydroxytryptamine （5-HT） and nerve growth factor （NGF） levels before and after treatment were detected， and the complications were recorded. Result:The clinical efficacy of the treatment group was superior to that of the control group （<italic>Z</italic>=2.079， <italic>P</italic><0.05）. Both VFSS and WST findings in the treatment group were milder than those in the control group （<italic>Z</italic>=2.004， <italic>P</italic><0.05 and <italic>Z</italic>=1.973， <italic>P</italic><0.05）. The VFSS， SWAL-QOL， and FOIS scores and the BDNF， DA， SP， 5-HT and NGF levels of the treatment group were elevated in contrast to those of the control group （<italic>P</italic><0.01）， whereas the NIHSS score declined （<italic>P</italic><0.01）. The complication rate in the treatment group was （8/58） 13.79%， significantly lower than （17/56） 30.36% in the control group （<italic>χ</italic>²=4.565， <italic>P</italic><0.05）. Conclusion:On the basis of balloon catheter dilatation and rehabilitation training， the Xingshen Tongqiao Huoxue decoction can significantly enhance the swallowing function， improve the quality of life， and reduce complications in patients with dysphagia caused by CPA after cerebral stroke.

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Several clinical therapies such as tissue repair by replacing injured tissues with functional ones have been reported; however, there is great potential for exploring traditional herbal-induced regeneration with good safety. Tongqiao Huoxue Decoction (TQHXD), a well-known classical traditional Chinese medicinal formula, has been widely used for clinical treatment of stroke. However, biological activity and mechanisms of action of its constituents toward conferring protection against cerebral ischemia-reperfusion (I/R) injury remain unclear. In this present study, we evaluated TQHXD quality using HPLC; then, it was screened for its potential active ingredients using a series of indices, such as their drug-likeness and oral bioavailability. Subsequently, we analyzed the potential mechanisms of TQHXD anti-I/R using gene ontology functional enrichment analyses. The network pharmacological approach enabled us to screen 265 common targets associated with I/R, indicating that TQHXD had remarkable protective effects on infarction volume, neurological function scores, and blood-brain barrier (BBB) injury. In addition, TQHXD significantly promoted the recovery of regional cerebral blood flow (rCBF) 7 days after reperfusion compared to rats in the vehicle group. Immunofluorescence results revealed a significantly higher CD34 expression in TQHXD-treated rats 7 days after reperfusion. TQHXD is not merely effective but eventually develops a secretory profile composed of VEGF and cerebral blood flow, a typical signature termed the angiogenesis-associated phenotype. Mechanistically, our data revealed that TQHXD (6 g/kg) treatment resulted in a marked increase in expression of p-focal adhesion kinase (FAK) and p-Paxillin proteins. However, Ki8751-mediated inhibition of VEGFR2 activity repealed its angiogenesis and protective effects and decreased both p-FAK and p-Paxillin protein levels. Taken together, these findings affirmed the potential of TQHXD as a drug for the management of stroke, which might be exerted by increasing the angiogenesis via the VEGF pathway. Therefore, these results provide proof-of-concept evidence that angiogenesis is a major contributor to TQHXD-treated I/R and that TQHXD is a promising traditional ethnic medicine for the management of this condition.

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Objective To investigate the clinical application of Tongqiao-Huoxue decoction for the treatment of vertebrobasilar artery insufficiency vertigo with stasis orifice type. Methods According to the random table method, 93 vertebrobasilar artery insufficiency vertigo patients with stasis orifice type were divided into the control group (n=46) and the treatment group (n=47). The patients in the control group were treated with fluoguizine hydrochloride, while the patients in the treatment group were treated with Tongqiao-Huoxue decoction on the basis of control group. Two groups were treated for 4 weeks. The clinical total effective rate of two groups of patients after treatment was compared. The LVA mean blood flow velocity, RVA mean blood flow velocity, BA mean blood flow velocity, total blood viscosity, plasma viscosity, erythrocyte aggregation index, fibrinogen, TC, TG, LDL-C and HDL-C were detected respectively before and after treatment. In addition, the adverse reaction incidence of two groups of patients were observed. Results The total effective rate of treatment group was 93.6% (44/47), while the total effective rate of control group was 78.3% (36/46). The difference between two groups was statistically significant (χ2=4.559, P=0.033). After treatment,the LVA mean blood flow velocity (38.34 ± 3.72 cm/s vs. 29.73 ± 3.11 cm/s, t=12.096), RVA mean blood flow velocity (41.12 ± 4.05 cm/s vs. 34.11 ± 3.86 cm/s, t=8.541),BA mean blood flow velocity (48.92 ± 5.24 cm/s vs. 40.75 ± 4.63 cm/s, t=7.962), HDL-C (2.13 ± 0.64 mmol/L vs. 1.54 ± 0.53 mmol/L, t=4.836) of treatment group were significantly higher than the control group (P<0.05), while the total blood viscosity, plasma viscosity, erythrocyteaggregation index, fibrinogen, TC, TG, LDL-C of treatment group were significantly lower than the control group (t value were 5.457, 8.875, 3.661, 6.549, 3.838, 6.369, 5.201, all Ps<0.05). No serious adverse reactions occurred during the treatment of the two groups. Conclusions The clinical curative effect of Tongqiao-Huoxue decoction for the treatment of vertebrobasilar artery insufficiency vertigo with stasis orifice type is significantly, and it can increases blood flow to the brain, improve hemorheology and lipid levels. It has the high security of the forward curative effect.

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The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.

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Calcio/metabolismo , Demencia Vascular/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Hipocampo/efectos de los fármacos , Discapacidades para el Aprendizaje/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Memoria/efectos de los fármacos , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Demencia Vascular/complicaciones , Demencia Vascular/metabolismo , Demencia Vascular/psicología , Medicamentos Herbarios Chinos/farmacología , Femenino , Hipocampo/metabolismo , Discapacidades para el Aprendizaje/etiología , Discapacidades para el Aprendizaje/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Fitoterapia , Ratas Sprague-Dawley , Transducción de Señal , Regulación hacia Arriba

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Objective To study the clinical curative effect of Tongqiao Huoxue decoction combined with edaravone and hyperbaric oxygen for treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods A prospective study was conducted. Forty-six patients with DEACMP admitted into Yidu Central Hospital of Weifang Medical College from January 2012 to January 2014 were randomly divided into observation group (23 cases) and control group (23 cases). The basic treatments of two groups were identical. Based on the basic treatments including hyperbaric oxygen and citicoline sodium injection etc, the observation group was treated with our-self made Tongqiao Huoxue decoction which could be modified in accord to the individual differentiation of syndromes in traditional Chinese medicine (the composition of decoction included Paeoniae Radix Rubra 15 g, Chuanxiong Rhizoma 15 g, Persicae Semen 15 g, Carthami Flos 15 g, Zingiberis Rhizoma Recens 3 pieces, Jujubae Fructus 2 pieces, Moschus 0.5 g, Allium Fistulosum 1 segment). The decoction was administered orally or by nasogastric gavage, one dosage everyday for 1 month, and in the mean time, edaravone intravenously drip 30 mg was given to the observation group twice a day for 14 days. The control group was given hyperbaric oxygen and other conventional treatment for 30 days. The clinical therapeutic effect and adverse reaction were observed after treatment for 30 days. The changes of intelligent level were detected by Hasegawa dementia scale (HDS), and the changes of latency of P300 were measured by electromyologram/evoked potential instrument in two groups before and after treatment. Results The total effective rate in observation group was significantly higher than that in control group [91.3% (21/23) vs. 65.2% (15/23), P < 0.01]. Elevation of creatinine occurred in 1 case, moderate increase in alanine aminotransferase (ALT) appeared in 1 case, and both of them were reduced to normal after treatment in observation group; no adverse reaction occurred in control group. The HDS scores were significantly higher 30 days after treatment than those before treatment in the two groups [control group:13.4±2.8 vs. 6.8±2.3, observation group:20.8±3.4 vs. 6.6±2.5, both P<0.05]. The latency of P300 after treatment was significantly lower in two groups than that before treatment [control group (ms): 355.7±25.7 vs. 385.5±27.8, observation group (ms): 337.3±24.6 vs. 386.8±25.4, both P < 0.05], the change in observation group being more significant [the HDS score: 20.8±3.4 vs. 13.4±2.8, the latency of P300 (ms): 337.3±24.6 vs. 355.7±25.7, both P<0.05]. Conclusion Tongqiao Huoxue decoction combined with edaravone and hyperbaric oxygen has favorable cognitive effect on patients with DEACMP, thus, it can be used extensively in clinic.

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OBJECTIVE: To study activity of tongqiao huoxue decoction (TQHXD) on memory and learning ability of rats with vascular dementia (VD) and its influence on fluorescence intensity of intracellular calcium concentration of hippocampal neurons. METHODS: Vascular dementia model was established by using improved bilateral carotid artery ligation method. The Morris water maze experiment was adopted to evaluate the ethology of VD rats. The fluorescence intensity of hippocampus intracellular calcium was detected by flow cytometry. RESULTS: Compared with the model group, high, middle and low dose group of TQHXD significantly reduce the time of escape latency and the distance of climbing on the platform (P < 0.01). The entries in the second quadrant, the times in the second quadrant and the distance in the second quadrant in relation to high, middle and low dose groups of TQHXD were increasing significantly (P < 0.05) and the latency to first entry in the second quadrant was shorten (P < 0.05). The fluorescence intensity of intracellular calcium in hippocampal neurons of the high, middle and low dose groups of TQHXD was lower than that of the model group (P < 0.01, P < 0.05). CONCLUSION: TQHXD can improve the memory and learning ability of rats with VD significantly. The mechanism may be related to reduce the intracellular calcium concentration in the hippocampus, thereby the damage of nerve cells is reduced.

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Objective To observe the effect of Tongqiao Huoxue decoction on the changes of motilin (MTL) and vasoactive intestinal peptide (VIP) and its protective effect on gastric mucosa in rats with cerebral infarction at acute stage.Methods According to random number table, 96 Wistar rats were divided into six groups: normal control, sham operation, cerebral infarction model, cimetidine, Tongqiao Huoxue decoction routine dose and low dose groups, eachn = 16. Cerebral infarction model group was established by using a suture to ligate the middle cerebral artery, resulting in its occlusion. The rats of cerebral infarction model group and sham operation group were lavaged with 2 mL of normal saline. Tongqiao Huoxue decoction routine dose group was lavaged with 2 mL of Tongqiao Huoxue decoction (1.3 g/mL), while Tongqiao Huoxue decoction low dose group was lavaged with 1 mL of Tongqiao Huoxue decoction (1.3 g/mL) plus 1 mL of normal saline. Cimetidine group was lavaged with cimetidine (0.1 g/kg), and nothing was done for the normal control group. On the 4th and 7th day after the delivery of treatment, inferior vena venous blood samples were collected to detect the plasma MTL and VIP concentrations. Then the gastric tissues were obtained and examined under an electron microscope.Results There were no statistically significant differences between the normal control group and sham operation group in plasma levels of MTL and VIP (bothP > 0.05). The plasma levels of MTL and VIP at 4 days and 7 days after the delivery of treatment in cerebral infarction model group were higher than those in the normal control group and sham operation group [4 days MTL (ng/L): 189.51±13.48 vs. 117.01±11.38, 117.67±12.73, VIP (ng/L): 94.86±4.14 vs. 60.98±5.42, 62.55±6.60, bothP < 0.05; 7 days: MTL (ng/L): 183.05±14.49 vs. 119.79±10.64, 120.27±11.48, VIP (ng/L): 91.92±3.77 vs. 59.63±4.29, 58.10±4.99, bothP < 0.05]. Plasma levels of MTL and VIP in cimetidine group, Tongqiao Huoxue decoction routine dose group and low dose group were significantly lower than those in cerebral infarction model group. Compared with Tongqiao Huoxue decoction low dose group and cimetidine group, the degrees of descent in plasma levels of MTL and VIP were apparently lower on the 7th day in Tongqiao Huoxue decoction routine dose group [MTL (ng/L): 138.72±8.02 vs. 152.16±12.66, 156.60±11.87, bothP < 0.05; VIP (ng/L):68.18±3.41 vs. 81.12±3.98, 78.89±2.13, bothP < 0.05]. The results of electron microscope: compared with normal control group and sham operation group, obvious pathological changes in gastric mucosa in model group were found. In Tongqiao Huoxue decoction routine group, Tongqiao Huoxue decoction low dose group and cimetidine group, the gastric mucosal lesions were milder, and the curative effects of Tongqiao Huoxue decoction routine group were much better.Conclusions During the acute stage of cerebral infarction, significant damage is seen in gastric mucosa in rats. Tongqiao Huoxue decoction not only can effectively regulate the expression levels of MTL and VIP, but also has certain protective effect on gastric mucosa, and its efficacy being directly proportional to the dosage.

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The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.

Asunto(s)

Animales , Femenino , Masculino , Calcio , Metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Metabolismo , Demencia Vascular , Quimioterapia , Metabolismo , Psicología , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Hipocampo , Metabolismo , Discapacidades para el Aprendizaje , Quimioterapia , Metabolismo , Aprendizaje por Laberinto , Memoria , Trastornos de la Memoria , Quimioterapia , Metabolismo , Fitoterapia , Ratas Sprague-Dawley , Transducción de Señal , Regulación hacia Arriba

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This study was aimed to explore the clinical efficacy and differences in hemorheological parameters in sudden deafness treated with Chinese medicine combined with electric acupuncture and western medicine . Patients were selected according to the diagnostic criteria of sudden deafness. Patients were randomly divided into the Chinese medicine combined with electric acupuncture group ( 35 cases ) and the western medicine group (30 cases). In the treatment group, Tongqiao Huoxue Decoction was orally administrated in combination with electric acupuncture on Jiaj i points on the neck region . In the western medicine group , alprostadil and prednisone were used . For both groups , 10 days were one treatment course . The results showed that after two treatment courses , the hearing improvement of two groups was compared . The total efficiency of Chinese medicine combined with electric acupuncture group was 91 . 4%. And the total efficiency of the western medicine group was 66 . 7%. There were significant differences between two groups ( P < 0 . 05 ) . The treatment efficiency of tinnitus between two groups was also compared . The total efficiency of Chinese medicine combined with electric acupuncture group was 91 . 2%. And the total efficiency of the western medicine group was 78 . 6%. There was no significant difference between two groups . The comparison of dizziness relieving effect between two groups showed that the total efficiency of Chinese medicine combined with electric acupuncture group was 94 . 1%; and the total efficiency of the western medicine group was 73 . 3%. There was no significant difference between two groups . The hemorheological parameters were also improved . In the Chinese medicine combined with electric acupuncture group , indexes such as blood viscosity ratio , plasma viscosity ratio , erythro-cyte electrophoresis time and hematocrit were all improved obviously compared to western medicine group . There was significant difference between two groups ( P < 0 . 05 ) . It was concluded that in the improvement of clinical symptoms of sudden deafness, physical signs and hemorheology, Chinese medicine combined with elec-tric acupuncture receives better effects compared to western medicine .

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OBJECTIVE: To study the activity of TQHXD on the learning and memory ability of rats with vascular dementia(VD) and its effects on the content of Ach in cerebral cortex. And to investigate the action mechanism of TQHXD on VD in rats. METHODS: VD model was made by common carotid artery injection of a co-thrombus inducer. The 8-arm radial maze experiment was adopted to evaluate the times of working memory errors and reference memory errors. The changes of the pathological area in hippocampus CA1 were observed by optical microscope. Enzyme-linked immunosorbent assay was used to determine the concentration of Ach in rats cerebral cortex. RESULTS: High and middle dose of TQXHD significantly reduce the times of working memory errors and reference memory errors (P<0.01), definitely improved the anormalies of pathological area in hippocampal CA1, and significantly increased the content of Ach in cerebral cortex (P<0.01). CONCLUSION: TQHXD can significantly ameliorate the learning and memory ability of in VD rats. The mechanism may be related to the improvement of the vertebral body cells anomalies in the hippocampal CA1 region and increasing the content of the Ach in cerebral cortex. Copyright 2012 by the Chinese Pharmaceutical Association.

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AIM: To investigate the protective effects and mechanisms of Tongqiao Huoxue Decoction on the rats of cerebral ischemia. METHODS: Cerebral ischemia madel was established on the basis of cerebral thrombus and at the same time ligaturing bilateral carotid arteries.These models were used to observe the protective effects of Tongqiao Huoxue Decoction on contents of CGRP、ET、IL-1?,TNF? in rats′ cerebral ischemica. RESULTS: The results showed that Tongqiao Huoxue Decoction decreased the contents of IL-1?、TNF-?、 ET,and increased the contents of CGRP. CONCLUSION: Tongqiao Huoxue Decoction had effects on anti-cerebral ischemia.The protective effects of Tongqiao Huoxue Decoction are related to decreasing the contents of IL-1?,TNF-?,ET,and increasing the contents of CGRP.